[4 + 3] Cycloaddition Chemistry of Allenamides
We have been examining extensively"the chemistry of 1-amidoallenes, or allenamides, and developed several major reactions associated with this new class of allenes. Most significantly, we achieved a tandem epoxidation and oxyallyl cation [4 + 3] cycloaddition using chiral allenamides. The epoxidation of allenamides proves to be an excellent source of chiral, nitrogen stabilized oxyallyl cations. We were able to develop highly regio- and stereoselective inter- and intramolecular oxyallyl cation [4 + 3] cycloadditions, and, very recently, we achieved the first asymmetric [4 + 3] cycloaddition using copper-bisoxazoline systems.
Stereoselective Methods Using Chiral Ynamides
In a related but different area, we have developed the chemistry of ynamides as stable equivalents of Ficini's ynamines. Our work has rekindled the interest of the synthetic community toward this very interesting class of functional group. We have placed particular emphasis on developing a highly efficient synthesis of ynamides in order to provide the kind of accessibility that may allow the community to view ynamides as a user-friendly functional group in organic synthesis. Toward this goal, we developed a Cu(II)-catalyzed C-N bond formation involving sp-hybridized carbons. This catalytic amidation provides a direct entry to chiral ynamides via N-alkynylation of amides and should have an impact on the future synthetic utility.
Natural Product Total Syntheses
We have developed a bio-inspired [3 + 3]-annulation reaction or formal cycloaddition of vinylogous amides or diketones with alpha,beta-unsaturated iminium salts that can be used to construct heterocycles]. The transformation involves a tandem Knoevenagel-6-pi-electron electrocyclic hetero ring-closure. This process has allowed us to achieve numerous total syntheses of complex natural products such as arisugacin A, tangutorine, hongoquercin A, perhydrohistrionicotoxin, cylindricines, and rhododaurichromanic acids.
Ketal-Tethered Reactions and Natural Product Syntheses
Ketal-tethered intramolecular reactions, specifically intramolecular Diels-Alder [IMDA] and RCM reactions, which are areas that have not been widely studied, are discussed here, as well as an approach to fusidilactone C and spirastrellolide A, spiroketal-containing natural products that first provoked our interest in ketal tethered strategies. These investigations are of significance because they can lead to conceptually and fundamentally different approaches to spiroketal-related complex natural products.